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Signet-ring cell adenoma of the thyroid and rheumatoid arthritis: incidental association or methotrexate-related change?

Adriana Handra-Luca

Data publikacji online: 2017/08/31
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Signet-ring cell change in thyroid adenoma is rarely reported [1–3]. We have recently seen such a tumour in a case of rheumatoid arthritis (RA) treated by methotrexate. Thyroid tumours are rarely reported in RA patients to our knowledge, mainly of carcinoma-type [4, 5]. The thyroid resection was performed for recent increase in size of a left thyroid nodule. At macroscopy, the nodule measured 1.5 × 2 cm. On microscopy, the nodule showed follicular hyperplasia of adenoma type (the entire specimen was analysed on microscopy). A thin fibrous capsule could be focally seen as well as intranodular fibrosis foci. The thyrocytes were disposed in vesicles or solid buds. They showed nuclear atypias. Several foci of signet-ring thyrocytes were located both close to and far from the intranodular fibrotic zones (Fig. 1).
The intracytoplasmic vacuoles were faintly stained with Alcian-blue, and PAS and were negative for the proteins detected by immunohistochemistry. TTF1 was diffusely expressed in the nuclei of adenoma thyrocytes. HBME1 was negative while CK19 and CD138/syndecan-1 were focally expressed, CD138 including in the signet-ring thyrocytes. CK7 was diffusely expressed while CK20 and CD25 were negative. CD56/NCAM was diffusely expressed in the adenoma thyrocytes, mainly with a membrane pattern including in the signet-ring thyrocytes. CD68, negative in the thyrocytes (vacuolated or not) was positive in rare xanthomatous foci (intranodular or extranodular, in thyroiditis-type lesions). The non-nodular thyroid showed multifocal lymphocytic thyroiditis foci, perivascular and/or perivesicular, with several intravesicular multinucleated giant cells. CD25 was expressed in sparse lymphocytes (isolated or in the lymphocytic foci). S100 (negative in the thyroid adenoma) was positive in intrathyroid perivascular neural fibres and in nerves. A solid-cystic, multifocal solid-cell-nest (SCN) was also observed, peculiar by the CD138 expression.
The main differential diagnosis was that of intra-adenoma metastasis of a signet-ring cell-type carcinoma, gastric or extragastric. The diffuse expression of TTF1, thyroglobulin and thyroperoxidase along with the lack of CK20 allowed us to rule out this hypothesis. Of note would be the expression of CD138 in the thyroid adenoma including in the signet-ring thyrocytes as well as the expression of CD56. The precise involvement of these proteins in cytoplasmic changes leading to vacuole formation is difficult to precise,...

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